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Trafficking of Serine/Threonine Kinase Receptors and Smad Activation

  • Christine Le Roy
  • Rohit Bose
  • Jeffrey L. Wrana
Part of the Proteins and Cell Regulation book series (PROR, volume 5)

Abstract

Signaling by the transforming growth factor-β (TGF-β) family of growth factors involves cell surface receptor serine/threonine kinases and downstream components such as SARA and Smurfs, which bind the receptor substrates called the Smad proteins. These components partition between two endocytic pathways, which lead to two separate functions in TGF-β signaling. On the one hand, clathrin-dependent endocytosis promotes signaling by leading the receptor to the early endosome where SARA is localized. On the other, non-clathrin pathways, which are enriched for the Smurf ubiquitin ligases, lead the receptor to degradation. However, in polarized cells, ligand addition induces TGF-β receptor trafficking into junctional regions of the cell where activation of Smad-dependent and -independent pathways mediates the process of epithelial-to-mesenchymal transition, which is critical during development and tumorigenesis. In this chapter, we will focus on how compartmentalization of TGF-β receptors and their downstream components controls TGF-β signaling and its biological functions

Keywords

caveolin EMT endocytosis Par6 polarity SARA Smurf TGF-β TGF-β receptor trafficking clathrin lipid-rafts 

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Copyright information

© Springer 2006

Authors and Affiliations

  • Christine Le Roy
    • 1
  • Rohit Bose
    • 1
  • Jeffrey L. Wrana
    • 1
  1. 1.Center for Systems Biology, Department of Medical Genetics and MicrobiologyUniversity of Toronto, Samuel Lunenfeld Research Institute, Mount Sinai HospitalTorontoCanada

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